Benzylidene ketal

Cat. I2, MeOH, rt, 24 h, >80% yield.Benzylidene ketals and thioketals are also cleaved under these conditions. 

As with the benzylidene ketals, the carbonate can be opened to give a monoprotected diol. ... 

Selective substitution may sometimes be achieved by indirect methods. Thus, treatment of 4,6-O-benzylidene acetals with cyanoborohydride and etheral hydrogen chloride converts than into the 6-O-benzyl ether, with a free hydroxyl group at the 4-position (see Chap. 3). Isopropylidene and benzylidene ketals are opened by trimethylaluminium to give good yields of a-hydroxy ten-butyl ethers, and a-hydroxy 1-phenylethyl ethers, respectively [5], The scope of the latter method has not yet been explored. 

In the absence of substituents at C-3, satisfactory diastercoselcctivity is obtained if the glycal has a rigid structure imparted by the protection of the C-4 and C-6 hydroxy groups as the benzylidene ketal, e.g., 2629. 

Cat. I2, MeOH, rt, 24h, >80% yield. Benzylidene ketals and thioketals are also cleaved under these conditions. The use of I2 in CH3CN/H2O cleaves terminal acetonides (90-95% yield) hut does not cleave MOM, PMB, Bn, allyl, and propargyl ethers. Silyl ethers are cleaved to some extent. ... 

The following abbreviations are used in this and the subsequent tables Ac for acetyl, Pr for propionyl, Bu for butyryl, Bz for benzoyl, Ts for tosyl, My for methylene, Ed for ethylidene, Bd for benzylidene, Fd for furfurylidene. Id for isopropylidene, Me for methyl, Et for ethyl, Be for benzyl, Tr for trityl and Az for azoyl. Where the linkages of acetals and ketals are known, they are shown by different type fonts.)... 

Acetals and ketals protect two hydroxyls at a time by forming either a 1,3-dioxane or a 1,3-dioxolane ring (Scheme 2.12). The most common ketal and acetal protecting groups are isopropylidene or acetonide and the benzylidene-type groups with... 

The usefulness of acetal or ketal groups can be exhibited in the following example (Scheme 2.30) Chien-Tien Chen et al. carried out a VO(OTf)2-catalyzed 4,6-0-benzylidene acetal protection of tetraol 107 with benzaldehyde to give the... 

In this section, consideration will be given to the actual processes of acetal- or ketal-formation and not to the more indirect methods by which acetals and ketals of the polyhydric alcohols may be synthesized from compounds (e.g. derivatives of the monosaccharides) containing preformed alkylidene or arylidene groupings. The condensation of a carbonyl compound with a glycol is facilitated by acidic catalysts, and, since the reaction is reversible, by dehydration. The catalysts most frequently employed are concentrated sulfuric, hydrochloric and hydro-bromic acids, gaseous hydrogen chloride, zinc chloride and cupric sulfate others are phosphorus pentoxide, sulfosalicylic acid, and anhydrous sodium sulfate. The formation of benzylidene compounds is promoted less efficiently by phosphorus pentoxide than by either concentrated sulfuric acid or concentrated hydrochloric acid 1" the reaction is assisted by chloro- and nitro-substituents on the aromatic nucleus, but hindered by methyl- and methoxy-groups.18... 

There are many references in the literature to experiments in which acetals and ketals of the polyhydric alcohols (and their derivatives) have been treated with reducing agents without there being any effect on the acetal and ketal groups. For example, 2,4-benzylidene-xylitol,66 2,4 3,5-(56) R. M. Haim, A. T. Ness and C. S. Hudson, J. Am. Chem. Soc., 66,1769 (1946). 

Hann, Hudson and their coworkers63 71 observed that the Hann-Hudson rules, although primarily based upon structures of known methylene acetals, were compatible with such of the structures of analogous benzylidene acetals as were then known. It was obvious when the rules were formulated that they did not apply at all to isopropylidene ketals. 

Methyl acetals and ketals are rapidly reduced to methyl ethers by sodium cyanoborohydride in methanol with dry HCI at ice temperatures. A dioxolane is completely cleaved to a methyl ether, showing intervention by the solvent at some stage (equation 14), but when an inert solvent such as THF is used only single cleavage occurs this reagent shows interesting selectivity in the reduction of benzylidene acetals in the carbohydrate series (see Section 1.9.3.4). 

The acid-catalysed formation of acetals and ketals of ascorbic acid is particularly useful for the. selective protection of the molecule whilst structural modification is being carried out. The 5,6-0-derivatives such as the isopropylidene ketal and benzylidene acetal are well known but, more recently, it has proved po.ssible to protect the C-2/C-3 positions selectively using particularly reactive aldehydes (Figure 4.14). This new development has paved the way for selective modification of the primary and secondary alcohol groupings on the ascorbic acid side chain. 

In order to selectively obtain the a-substituted condensation products from levulinate esters, it is necessary to protect the ketone group. Ethyl levulinate reacts with one mole of ethylene glycol to form the cyclic ketal. Condensation of the protected ester with benzaldehyde gave the a-benzylidene ester in 73% yield (Figure 3). 

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